The acute Leukemias are clonal

hematopoietic malignant disease

that arise from the malignant

T r a n s f o r m a t i o n of an

early Hematopoietic stem cell.

The acute LeukemiaThe acute Leukemia

Dr.Azarm

Known risk factors for leukemiaKnown risk factors for leukemia

High dose radiation exposure

Occupational exposure to benzene

Prior chemotherapy especially alkylating agents

Chromosomal instability disorders, such as - Bloom’s syndrome,- Fanconi’s anemia, - Downs syndrome, - Ataxia telangiectasia.

Dr.Azarm

Acute leukemiais are classified by cell linesgeAcute leukemiais are classified by cell linesgeinto (1) acute myelogenous leukemia (AML) orinto (1) acute myelogenous leukemia (AML) or(2) acute lymphoblastic leukemia (ALL) based on:(2) acute lymphoblastic leukemia (ALL) based on:

- Morphology

- Cytogenetics

- Cell surface

-Cytoplasmic markers

-Molecular studiesDr.Azarm

Complication of LeukemiaComplication of Leukemia

-Bone Marrow failure Anemia , Leukopenia, Thrombocytopenia-Infection-Bleeding -Blast infiltration in: Bone Marrow Pripheral Blood Lymph nodes spleen Liver Skin Meningeal Other Organs

FAB Classification of acute LeukemiaFAB Classification of acute Leukemia

Acute Myeloblastic Leukemia

M1- Acute Myeloblastic L. without differentiation

M2- A.M.L.with diferentiation (predominantly Myloblast & promyeloblast

M3- Acute promyeloblatic leukemia

M4- Acute Myelomonocytic leukemia

M5- Acute Monocytic Leukemia

M6- Erythroleukemia

M7- Megakariocytic Leukemia

Acute Lymphoblastic Leukemia

L1- Small cells,Homogeneous population,childhood variant. L2- Larger L. Heterogeneous population, adult variant

L3- Burkitt-like Large cells ,Vacuolated cytoplasm

Cytogenetics in AMLCytogenetics in AML

t(15;17) in M3

t(8;21) in M2

Inv(16) in M4 Eo, are associated with better prognosis.

Monosomy 7 and multiple breakages , ( poor prognosis ) .

Investigation and diagnosis

FBC and PB film

Bone marrow aspiration and biopsy

High WBC with Blast , but may be low.

Platelet & Hb usually low

Marrow with Blast infiltrated >30%

Immunophenotyping and Karyotyping allows classification

Supportive treatmentSupportive treatment

- Give explanation and offer counselling

- RBC and platelet transfusion

- Start hydration and Allopurinol Po

- Insert tunnelled central venous ccatheter

- Start neutropenic regimen and prophylaxis

Specific treatment in AMLSpecific treatment in AML-Treatment protocols are age related; patients. 60y only tolerate less intensive treat and very rarely transplant

Supportive treatment alone is a valid treatment option in the >75 age group

Outline treatment for patients <60y is 4- 5 courses of intensive combination chemotherapy each 5-10 days with 2- 3 w .

Allogeneic or autologous stem cell transplantation are option for younger patients

Major complication are infection , Bacterial , Fungal, Viral.

In the longer term , relapse is the main complication .

Prognosis of AMLPrognosis of AML

Worst prognosis group: <10% chance cure:- Age >60y

- High WBC

- >20% blast after chemotherapy course 1- CNS disease

Good prognosis group : > 60% chance cure:

- Young patients<30- T(15;17)- M3 subtype

Treatment plan for ALL

2 phase induction chemotherapy to induce remission

2 or 4 intensification + intrathecal methotrexate or CNS radiation

Maintenance therapy for 2 y (out patient oral chemotherapy)

Transplant options:

- Allogeneic and autologous for child who relapse after CR.

Adult in first CR < 60 y especially if philadelphia positive.

Prognosis of ALLPrognosis of ALL

Childhood ALL has a cure rate of > 70%

up to 90% in the best prognostic group ie girls

Aged 1- 10y with low WBC , no CNS disease

and absence of Ph chromosome who achieve

CR after first phase induction chemotherapy.

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